Without cartilage — a pliable, supportive tissue found throughout the body — bones would rub up against one another at joints, causing limited movement and pain. Unfortunately, this is what happens when adults lose cartilage, since humans lose the ability to regenerate cartilage after age 18. “If there is an injury or if there is degeneration as a result of a special condition like osteoarthritis or something else, the tissue is unable to regrow,” said Samuel Stupp, a materials scientist at Northwestern University.
To fill in missing cartilage, Stupp’s team has been pioneering the development of new biomaterials that mimic the structure of the extracellular matrix (ECM) — with the goal to create a scaffold that is both biologically active and compatible with real tissue to promote regeneration. In a recent study, they designed a slurry-like material with nanoscale filaments that send signals inviting stem-like cells to migrate into it and make new cartilage (1). The nanoscale filaments are made out of peptide amphiphile molecules that self-assemble into bundles, where they bind hyaluronic acid molecules and transforming growth factor β-1 (TGFβ-1) that signals to nearby cells. Once it’s injected and comes into contact with calcium ions, the material transforms into a rubbery 3D structure where new cartilage grows to fill it in — and then the biomaterial disappears entirely. “The material is completely biodegradable,” said Stupp. “It doesn't leave any trace.”
By injecting the new biomaterial into sheep (a large-animal model that closely models human joints), the research team found that their scaffold initiated regeneration of the articular cartilage that covers and protects the ends of bones. “We were pleasantly surprised that it worked in sheep,” said Stupp, adding that they verified that the newly regenerated cartilage was comprised of the expected biopolymers found in normal cartilage ECM.
Now, Stupp’s team hopes to move their bioactive scaffold closer to patients. First, they plan to tweak its chemistry in ways that will make it easier to manufacture on a large scale for hospitals. “We are hoping to bring it to the clinic, optimize it, make sure that it is the best possible product, and then get permission from the FDA for the first clinical trial,” said Stupp.
Stupp added that unlike most prior interventions to repair joints, he believes that the Food and Drug Administration (FDA) should evaluate the scaffold as a combination product that is part device and part drug. “In this case, the material actually has molecules that interact directly with cells by design. So, there's a communication with cells, which is the way all drugs operate.”
Reference
- Lewis, J.A. et al. A bioactive supramolecular and covalent polymer scaffold for cartilage repair in a sheep model. Proc Natl Acad Sci USA 121, e2405454121 (2024).
